During in vitro fertilization (IVF), fertility patients are expected to self-administer many injections as part of this treatment. While newer medications have been developed to substantially reduce the number of these injections, such agents are typically much more expensive. Considering these differences in both cost and number of injections, this study compared patient preferences between GnRH-agonist and GnRH-antagonist based protocols in IVF.
Data were collected by voluntary, anonymous questionnaire at first consultation appointment. Patient opinion concerning total number of s.c. injections as a function of non-reimbursed patient cost associated with GnRH-agonist [A] and GnRH-antagonist [B] protocols in IVF was studied.
Completed questionnaires (n = 71) revealed a mean +/− SD patient age of 34 +/− 4.1 yrs. Most (83.1%) had no prior IVF experience; 2.8% reported another medical condition requiring self-administration of subcutaneous medication(s). When out-of-pocket cost for [A] and [B] were identical, preference for [B] was registered by 50.7% patients. The tendency to favor protocol [B] was weaker among patients with a health occupation. Estimated patient costs for [A] and [B] were $259.82 +/− 11.75 and $654.55 +/− 106.34, respectively (p < 0.005). Measured patient preference for [B] diminished as the cost difference increased.
This investigation found consistently higher non-reimbursed direct medication costs for GnRH-antagonist IVF vs. GnRH-agonist IVF protocols. A conditional preference to minimize downregulation (using GnRH-antagonist) was noted among some, but not all, IVF patient sub-groups. Compared to IVF patients with a health occupation, the preference for GnRH-antagonist was weaker than for other patients. While reducing total number of injections by using GnRH-antagonist is a desirable goal, it appears this advantage is not perceived equally by all IVF patients and its utility is likely discounted heavily by patients when nonreimbursed medication costs reach a critical level.
GnRH-antagonist; IVF; Preference; Patient cost; Health economics
During IVF, non-transferred embryos are usually selected for cryopreservation on the basis of morphological criteria. This investigation evaluated an application for array comparative genomic hybridization (aCGH) in assessment of surplus embryos prior to cryopreservation.
First-time IVF patients undergoing elective single embryo transfer and having at least one extra non-transferred embryo suitable for cryopreservation were offered enrollment in the study. Patients were randomized into two groups: Patients in group A (n=55) had embryos assessed first by morphology and then by aCGH, performed on cells obtained from trophectoderm biopsy on post-fertilization day 5. Only euploid embryos were designated for cryopreservation. Patients in group B (n=48) had embryos assessed by morphology alone, with only good morphology embryos considered suitable for cryopreservation.
Among biopsied embryos in group A (n=425), euploidy was confirmed in 226 (53.1%). After fresh single embryo transfer, 64 (28.3%) surplus euploid embryos were cryopreserved for 51 patients (92.7%). In group B, 389 good morphology blastocysts were identified and a single top quality blastocyst was selected for fresh transfer. All group B patients (48/48) had at least one blastocyst remaining for cryopreservation. A total of 157 (40.4%) blastocysts were frozen in this group, a significantly larger proportion than was cryopreserved in group A (p=0.017, by chi-squared analysis).
While aCGH and subsequent frozen embryo transfer are currently used to screen embryos, this is the first investigation to quantify the impact of aCGH specifically on embryo cryopreservation. Incorporation of aCGH screening significantly reduced the total number of cryopreserved blastocysts compared to when suitability for freezing was determined by morphology only. IVF patients should be counseled that the benefits of aCGH screening will likely come at the cost of sharply limiting the number of surplus embryos available for cryopreservation.
Fertilization in vitro; Comparative genomic hybridization; Preimplantation genetic diagnosis; Cryopreservation
To report on relationships among baseline serum anti-Müllerian hormone (AMH) measurements, blastocyst development and other selected embryology parameters observed in non-donor oocyte IVF cycles.
Pre-treatment AMH was measured in patients undergoing IVF (n = 79) and retrospectively correlated to in vitro embryo development noted during culture.
Mean (+/- SD) age for study patients in this study group was 36.3 ± 4.0 (range = 28-45) yrs, and mean (+/- SD) terminal serum estradiol during IVF was 5929 +/- 4056 pmol/l. A moderate positive correlation (0.49; 95% CI 0.31 to 0.65) was noted between basal serum AMH and number of MII oocytes retrieved. Similarly, a moderate positive correlation (0.44) was observed between serum AMH and number of early cleavage-stage embryos (95% CI 0.24 to 0.61), suggesting a relationship between serum AMH and embryo development in IVF. Of note, serum AMH levels at baseline were significantly different for patients who did and did not undergo blastocyst transfer (15.6 vs. 10.9 pmol/l; p = 0.029).
While serum AMH has found increasing application as a predictor of ovarian reserve for patients prior to IVF, its roles to estimate in vitro embryo morphology and potential to advance to blastocyst stage have not been extensively investigated. These data suggest that baseline serum AMH determinations can help forecast blastocyst developmental during IVF. Serum AMH measured before treatment may assist patients, clinicians and embryologists as scheduling of embryo transfer is outlined. Additional studies are needed to confirm these correlations and to better define the role of baseline serum AMH level in the prediction of blastocyst formation.
serum AMH; IVF; embryo development; blastocyst transfer
Guidelines for safe gamete donation have emphasised donor screening, although none exist specifically for testing oocyte recipients. Pre-treatment assessment of anonymous donor oocyte IVF treatment in Ireland must comply with the European Union Tissues and Cells Directive (Directive 2004/23/EC). To determine the effectiveness of this Directive when applied to anonymous oocyte recipients in IVF, we reviewed data derived from selected screening tests performed in this clinical setting.
Data from tests conducted at baseline for all women enrolling as recipients (n = 225) in the anonymous oocyte donor IVF programme at an urban IVF referral centre during a 24-month period were analysed. Patient age at programme entry and clinical pregnancy rate were also tabulated. All recipients had at least one prior negative test for HIV, Hepatitis B/C, chlamydia, gonorrhoea and syphilis performed by her GP or other primary care provider before reproductive endocrinology consultation.
Mean (±SD) age for donor egg IVF recipients was 40.7 ± 4.2 yrs. No baseline positive chlamydia, gonorrhoea or syphilis screening results were identified among recipients for anonymous oocyte donation IVF during the assessment interval. Mean pregnancy rate (per embryo transfer) in this group was 50.5%.
When tests for HIV, Hepatitis B/C, chlamydia, gonorrhoea and syphilis already have been confirmed to be negative before starting the anonymous donor oocyte IVF sequence, additional (repeat) testing on the recipient contributes no new clinical information that would influence treatment in this setting. Patient safety does not appear to be enhanced by application of Directive 2004/23/EC to recipients of anonymous donor oocyte IVF treatment. Given the absence of evidence to quantify risk, this practice is difficult to justify when applied to this low-risk population.
Purpose: Tripronucleate (3pn) development after conventional insemination (CONV) or ICSI was analyzed to estimate the rate of second polar body retention giving rise to 3pn formation.
Methods: Data from 453 consecutive IVF cycles were reviewed during a 6-month period. Mature oocytes were monitored in ICSI (n = 3195) and CONV (n = 2274) groups by fertilization assessment 16–18 h post-insemination. Ovulation induction protocols and in vitro culture conditions remained constant during the study interval.
Results: Normal (2pn) fertilization occurred in 74.2% and 70.5% for CONV and ICSI groups, respectively (p < 0.003). 1pn formation was observed in 4.5% of CONV oocytes, and 2.5% of ICSI oocytes (p < 0.001); 3pn formation was 8.1% in the CONV group, and 2.5% in the ICSI group (p < 0.0001). We observed 4pn formation in 0.4% of oocytes in the CONV group, but in only 0.04% of oocytes fertilized with ICSI (p < 0.007). Cellular degeneration occurred in 2.4% of oocytes inseminated conventionally, and in 3.5% of oocytes fertilized by ICSI (p = 0.02). Maternal age did not impact pronuclear status.
Conclusions: We found the 3pn formation rate after ICSI to be approximately one-third that observed in the CONV group. Extrapolating the ICSI data to the CONV data, it may be inferred that 2.5% of 3pn development after CONV was due to second polar body retention. This suggests that 5.6% of CONV oocytes showed dispermic fertilization. Decreasing oocyte quality with increasing maternal age had no apparent influence on any of the fertilization outcomes.
Fertility; fertilization; oocyte; reproductive techniques
To describe pre- and post-methotrexate (MTX) therapy images from pelvic magnetic resonance imaging (MRI) with gadopentetate dimeglumine contrast following chemotherapy for post-partum hemorrhage secondary to placenta increta.
Material and method
A 28-year-old Caucasian female presented 4 weeks post-partum complaining of intermittent vaginal bleeding. She underwent dilatation and curettage immediately after vaginal delivery for suspected retained placental tissue but 28 d after delivery, the serum β-hCG persisted at 156 IU/mL. Office transvaginal sonogram (4 mHz B-mode) was performed, followed by pelvic MRI using a 1.5 Tesla instrument after administration of gadolinium-based contrast agent. MTX was administered intramuscularly, and MRI was repeated four weeks later.
While transvaginal sonogram suggested retained products of conception confined to the endometrial compartment, an irregular 53 × 34 × 28 mm heterogeneous intrauterine mass was noted on MRI to extend into the anterior myometrium, consistent with placenta increta. Vaginal bleeding diminished following MTX treatment, with complete discontinuation of bleeding achieved by ~20 d post-injection. MRI using identical technique one month later showed complete resolution of the uterine lesion. Serum β-hCG was <5 IU/mL.
Reduction or elimination of risks associated with surgical management of placenta increta is important to preserve uterine function and reproductive potential. For selected hemodynamically stable patients, placenta increta may be treated non-operatively with MTX as described here. A satisfactory response to MTX can be ascertained by serum hCG measurements with pre- and post-treatment pelvic MRI with gadopentetate dimeglumine enhancement, which offers advantages over standard transvaginal sonography.
magnetic resonance imaging; placenta increta; methotrexate
The promise of medical innovation has long evoked social commentary, particularly when personal reproductive autonomy may be involved. Development of the oral contraceptive, effective and safe surgical sterilization, and later IVF and ICSI are among the revolutionary developments where the initial reactions were dubious but were accorded mainstream status with sufficient clinical experience. In each instance, debate about the moral and social implications of these treatments accompanied their introduction into the medical marketplace. This pattern appears to be repeating itself in connection with the use of preimplantation genetic diagnosis (PGD) for elective sex selection of human embryos. As with prior challenges in reproductive medicine, the development of meaningful “guidelines” for this latest controversy has proven to be a contentious task. Indeed, the progression of ethics committee reports from the Society for Reproductive Medicine seems to echo the ambivalence within society at large regarding this issue. In this report, we chronicle sex selection claims based on sperm sorting, and describe how flow cytometry and especially PGD have facilitated this selection at the gamete and embryo stage, respectively. In doing so, we also explore market forces and practitioner considerations associated with the application of PGD for this; related ethical issues with particular emphasis on the progeny derived from such treatment are also.
Ethics; IVF; PGD; sex selection
We present a case of monochorionic-triamniotic pregnancy that developed after embryo transfer following in vitro fertilization (IVF).
After controlled ovarian hyperstimulation and transvaginal retrieval of 22 metaphase II oocytes, fertilization was accomplished with intracytoplasmic sperm injection (ICSI). Assisted embryo hatching was performed, and two embryos were transferred in utero. One non-transferred blastocyst was cryopreserved.
Fourteen days post-transfer, serum hCG level was 423 mIU/ml and subsequent transvaginal ultrasound revealed a single intrauterine gestational sac with three separate amnion compartments. Three distinct foci of cardiac motion were detected and the diagnosis was revised to monochorionic-triamniotic triplet pregnancy. Antenatal management included cerclage placement at 19 weeks gestation and hospital admission at 28 weeks gestation due to mild preeclampsia. Three viable female infants were delivered via cesarean at 30 5/7 weeks gestation.
The incidence of triplet delivery in humans is approximately 1:6400, and such pregnancies are classified as high-risk for reasons described in this report. We also outline an obstetric management strategy designed to optimize outcomes. The roles of IVF, ICSI, assisted embryo hatching and associated laboratory culture conditions on the subsequent development of monozygotic/monochorionic pregnancy remain controversial. As demonstrated here, even when two-embryo transfer is employed after IVF the statistical probability of monozygotic multiple gestation cannot be reduced to zero. We encourage discussion of this possibility during informed consent for the advanced reproductive technologies.
triplet pregnancy / IVF / monochorionic / cerclage / outcome
We present a case of primary infertility related to extreme cervical stenosis, a subset of cervical factor infertility which accounts for approximately 5% of all clinical infertility referrals.
A 37 year-old nulligravida was successfully treated with ovulation induction via recombinant follicle stimulating hormone (FSH) and direct intraperitoneal insemination (IPI). Anticipating controlled ovarian hyperstimulation with in vitro fertilization/embryo transfer (IVF), the patient underwent hysteroscopy and cervical recanalization, but safe intrauterine access was not possible due to severe proximal cervical stricture. Hysterosalpingogram established bilateral tubal patency and confirmed an irregular cervical contour. Since the cervical canal could not be traversed, neither standard intrauterine insemination nor transcervical embryo transfer could be offered. Prepared spermatozoa were therefore placed intraperitoneally at both tubal fimbria under real-time transvaginal sonographic guidance using a 17 gage single-lumen IVF needle. Supplementary progesterone was administered as 200 mg/d lozenge (troche) plus 200 mg/d rectal suppository, maintained from the day following IPI to the 8th gestational week. A singleton intrauterine pregnancy was achieved after the second ovulation induction attempt.
In this report, we outline the relevance of cervical factor infertility to reproductive medicine practice. Additionally, our andrology evaluation, ovulation induction approach, spermatozoa preparation, and insemination technique in such cases are described.
cervical factor infertility; intraperitoneal insemination; ovulation induction
Our investigation sought to compare changes in sexual function following supracervical hysterectomy (SCH) and total abdominal hysterectomy (TAH).
A retrospective chart review was performed to identify all patients who underwent supracervical hysterectomy or total abdominal hysterectomy at a tertiary care center. Patients who met criteria for participation were sent a one page confidential, anonymous questionnaire to assess sexual function experienced both pre- and postoperatively. A total of 69 patients in each group were eligible for participation. A multiple logistic regression model was used to analyze measured variables.
Forty-eight percent (n = 33) of women undergoing a SCH returned the questionnaire, while 39% (n = 27) of those undergoing a TAH chose to participate. There were no significant demographic differences between the two groups. Patients who underwent TAH reported worse postoperative sexual outcome than SCH patients with respect to intercourse frequency, orgasm frequency and overall sexual satisfaction (P = 0.01, 0.03, and 0.03, respectively). Irrespective of type of hysterectomy, 35% of patients who underwent bilateral salpingoophorectomy (BSO) with hysterectomy experienced worse overall sexual satisfaction compared to 3% of patients who underwent hysterectomy alone (P = 0.02).
Our data suggest that TAH patients experienced worse postoperative sexual function than SCH patients with respect to intercourse frequency and overall sexual satisfaction. Irrespective of type of hysterectomy, patients who underwent bilateral salpingoophorectomy experienced worse overall sexual satisfaction.
This investigation was undertaken to describe patient perception and awareness of the polycystic ovary syndrome (PCOS), the most common cause of anovulation/oligoovulation among women of reproductive age.
Fifteen parameters were evaluated by a computer-based research instrument accessed by a large, unscreened population. Incomplete questionnaires were not entered, and responses were electronically tabulated to block duplicate submissions.
From 657 participants, the majority (63%) were between 26–34 years old; mean BMI was 30.4 kg/m2. 343 of 657 had at least one pregnancy and 61% of the study group had taken fertility medicine (any type) at least once. Physicians were the most common provider of PCOS information for all study participants, irrespective of age. Patient emotions associated with the diagnosis of PCOS included "frustration" (67%), "anxiety" (16%), "sadness" (10%), and "indifference" (2%). Self-reported patient aptitude regarding PCOS was scored as high or "very aware" in >60% of women. Respondents were also asked: "If your PCOS could be safely and effectively helped by something else besides fertility drugs or birth control pills, would that interest you?" Interest in alternative PCOS treatments was expressed by 99% of the sample (n = 648).
In our study population, most women associated negative emotions with PCOS although the self-reported knowledge level for the disorder was high. While these women regarded their obstetrician-gynecologist as integral to their PCOS education, traditional PCOS therapies based on oral contraceptives or ovulation induction agents were regarded as unsatisfactory by most women.
Purpose:Our purpose was to determine if the presence of a hydrosalpinx effects the outcome of in vitro fertilization (IVF)–embryo transfer.
Methods:We performed a retrospective analysis of IVF cycle stimulation sheets.
Results:A total of 1000 patients with tubal factor infertility was analyzed. There were 60 hydrosalpinx patients who underwent 116 initiated cycles with 106 embryo transfers, compared to 940 control patients undergoing 1428 initiated cycles with 1150 embryo transfers. Both groups had a similar response to ovarian stimulation, number of oocytes retrieved, and number of embryos transferred. The hydrosalpinx group had a significantly higher preclinical loss rate (22/59 = 37% vs 80/566 = 14%; P = 0.001), a significantly lower implantation rate (55/352 = 16% vs 795/3795 = 21%; P = 0.013), a trend toward a reduced delivery rate per transfer (28/106 = 26% vs 387/1150 = 34%; P = 0.066), a significantly higher ectopic pregnancy rate (5/59 = 8% vs 16/566 = 3%; P = 0.04), and a similar spontaneous abortion rate (9/37 = 24% vs 99/486 = 20%; P = 0.28) compared to the control tubal factor group.
Conclusions:This study demonstrates a decrease in implantation rates and an increase in preclinical miscarriages and ectopic pregnancies in patients with hydrosalpinges compared to tubal-factor patients without sonographic evidence of dilated fallopian tubes.
hydrosalpinx; in vitro fertilization; ectopic pregnancy; implantation
To describe practice trends for total abdominal hysterectomy (TAH) and supracervical abdominal hysterectomy (SCH) in New York State and to identify fiscal features associated with these two operations, all inpatient discharges for TAH and SCH performed for benign indications from 1990 to 1996 were reviewed using the Statewide Planning and Resource Cooperative System, a centralized data reporting system. For each year examined, the number of TAHs and SCHs performed, the procedure rates adjusted for the total New York State female population, and theper diem charge (calculated from mean institutional charge as a function of average length of stay) were evaluated. While the TAH rate declined in New York State, from 34.0 in 1990 to 28.4 in 1996 (P=.01), the SCH rate increased nearly five-fold during the same period, from 0.62 to 3.07 (P=.0003). Patients tended to be discharged later following SCH than for TAH, although by 1996, the LOS for both operations was equivalent. Theper diem institutional charge for SCH was consistently higher than for TAH in each year studied. The changes in charge and relative frequency of TAH and SCH in New York State invite further study to describe these trends more fully.
Hysterectomy; Supracervical trends; Surgical practice
Single embryo transfer (SET) remains underutilized as a strategy to reduce multiple gestation risk in IVF, and its overall lower pregnancy rate underscores the need for improved techniques to select one embryo for fresh transfer. This study explored use of comprehensive chromosomal screening by array CGH (aCGH) to provide this advantage and improve pregnancy rate from SET.
First-time IVF patients with a good prognosis (age <35, no prior miscarriage) and normal karyotype seeking elective SET were prospectively randomized into two groups: In Group A, embryos were selected on the basis of morphology and comprehensive chromosomal screening via aCGH (from d5 trophectoderm biopsy) while Group B embryos were assessed by morphology only. All patients had a single fresh blastocyst transferred on d6. Laboratory parameters and clinical pregnancy rates were compared between the two groups.
For patients in Group A (n = 55), 425 blastocysts were biopsied and analyzed via aCGH (7.7 blastocysts/patient). Aneuploidy was detected in 191/425 (44.9%) of blastocysts in this group. For patients in Group B (n = 48), 389 blastocysts were microscopically examined (8.1 blastocysts/patient). Clinical pregnancy rate was significantly higher in the morphology + aCGH group compared to the morphology-only group (70.9 and 45.8%, respectively; p = 0.017); ongoing pregnancy rate for Groups A and B were 69.1 vs. 41.7%, respectively (p = 0.009). There were no twin pregnancies.
Although aCGH followed by frozen embryo transfer has been used to screen at risk embryos (e.g., known parental chromosomal translocation or history of recurrent pregnancy loss), this is the first description of aCGH fully integrated with a clinical IVF program to select single blastocysts for fresh SET in good prognosis patients. The observed aneuploidy rate (44.9%) among biopsied blastocysts highlights the inherent imprecision of SET when conventional morphology is used alone. Embryos randomized to the aCGH group implanted with greater efficiency, resulted in clinical pregnancy more often, and yielded a lower miscarriage rate than those selected without aCGH. Additional studies are needed to verify our pilot data and confirm a role for on-site, rapid aCGH for IVF patients contemplating fresh SET.